承認前に開発中止になったファシグリファムの非臨床薬物動態試験成績

DOI
  • 小亀 暁史
    Axcelead Drug Discovery Partners株式会社 研究本部 薬物動態分析
  • 田川 吉彦
    Axcelead Drug Discovery Partners株式会社 研究本部 薬物動態分析
  • Liping PAN
    武田 グローバル ディベロップメントセンター
  • 森 郁生
    武田薬品工業株式会社 リサーチ 薬剤安全性研究所
  • 守屋 優
    武田薬品工業株式会社 リサーチ 薬物動態研究所
  • 蛯原 卓哉
    Axcelead Drug Discovery Partners株式会社 研究本部 薬物動態分析
  • 諸橋 昭雄
    株式会社ネモトサイエンス
  • 福井 英夫
    Axcelead Drug Discovery Partners株式会社 研究本部 非臨床安全性研究
  • Leslie Z. BENET
    カリフォルニア大学サンフランシスコ校薬学部

書誌事項

タイトル別名
  • Nonclinical pharmacokinetics of Fasiglifam, the G protein-coupled receptor 40 agonist for treatment of type 2 diabetes mellitus, discontinued prior to approval

抄録

<p>Fasiglifam (TAK-875), a GPR40 agonist, which was under development as a type 2 diabetes agent, voluntarily discontinued the development just before NDA in Japan and the US. The cause of discontinuation was the concern of side effects on human liver, which were recognized as Drug Induced Liver Injury (DILI). In fact, various groups have studied the cause of DILI induction by Fasiglifam; however, due to the complexity of its development mechanism, the extrapolation and predictability from animals to humans have not been sufficiently elucidated.</p><p>DILI in humans by fasiglifam was not a phenomenon unexpectedly clarified in the clinical trial, but the influence on liver effect of dogs had been confirmed from the early development stage. In fact, FDA asked for a view on the extrapolation of dog hepatotoxicity to humans, and they requested a prospective for human safety after the initiation of Phase 3.</p><p>The results of various nonclinical studies eliminated the concern of extrapolation to humans related to the dog hepatotoxicity and the initiation of Phase 3 trial was approved by FDA.</p><p>In this symposium, I would like to share the results of nonclinical DMPK studies that wiped out the concerns about human extrapolation on hepatotoxicity in dogs, and consider whether the judgment was appropriate. Also, I would like to consider the relationship between dog hepatotoxicity and adverse effects of human liver in the Phase 3 trial which actually decided to discontinue the development voluntarily.</p>

収録刊行物

詳細情報 詳細情報について

  • CRID
    1390845713082786304
  • NII論文ID
    130007677625
  • DOI
    10.14869/toxpt.46.1.0_s8-2
  • 本文言語コード
    ja
  • データソース種別
    • JaLC
    • CiNii Articles
  • 抄録ライセンスフラグ
    使用不可

問題の指摘

ページトップへ